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Guidelines for Authors Revised May 2015

Major Changes for 2015

Section 2.1.9 Interference Compounds added.

Section 2.3.2 Purity of Tested Compounds addition of qHNMR protocol as evidence of

purity.

Contents (click on the topic) 1 Scope and Editorial Policy

1.1 Scope of the Journal 1.2 Manuscript Categories

1.2.1 Articles 1.2.2 Brief Articles 1.2.3 Perspectives 1.2.4 Drug Annotations 1.2.5 Viewpoint 1.2.6 Featured Articles

1.3 Prior Publication 1.4 Patents and Intellectual Property 1.5 Professional Ethics 1.6 Issue Frequency

2 Preparing the Manuscript 2.1 General Considerations

2.1.1 Articles 2.1.2 Brief Articles 2.1.3 Perspectives 2.1.4 Drug Annotations 2.1.5 Viewpoint 2.1.6 Nomenclature 2.1.7 Compound Code Numbers 2.1.8 Trademark Names 2.1.9 Interference Compounds

2.2 Manuscript Organization 2.2.1 Title Page 2.2.2 Abstract 2.2.3 Introduction 2.2.4 Results 2.2.5 Discussion and Conclusions 2.2.6 Experimental Section 2.2.7 Ancillary Information 2.2.8 References and Notes 2.2.9 Tables

2.2.10 Figures, Schemes/Structures, and Charts 2.2.11 Image Manipulation 2.2.12 Table of Contents Graphic 2.2.13 Supporting Information 2.2.14 Molecular Formula Strings

2.3 Specialized Data 2.3.1 Biological Data 2.3.2 Purity of Tested Compounds 2.3.3 Confirmation of Structure 2.3.4 Combinatorial Chemistry 2.3.5 Computational Chemistry 2.3.6 QSAR/QSPR and Proprietary Data 2.3.7 Statistical Criteria 2.3.8 Software 2.3.9 Structural Data 2.3.10 Compound Characterization Checklist

3 Submitting the Manuscript 3.1 Paragon Plus Web Site 3.2 Cover Letter 3.3 Conflict of Interest Disclosure 3.4 Journal Publishing Agreement 3.5 Author List 3.6 Funding Sources 3.7 ORCID 3.8 Revision 3.9 Proofs 3.10 ACS Policies for E-prints and Reprints 3.11 Just Accepted Manuscripts 3.12 Post Acceptance and ASAP Publication 3.13 Corrections 3.14 Retractions

4 Standard Abbreviations and Acronyms

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1 Scope and Editorial Policy

1.1 Scope of the Journal

The Journal of Medicinal Chemistry (Journal) invites original research contributions dealing

with chemical-biological relationships. The primary objective of the Journal is to publish studies

that contribute to an understanding of the relationship between molecular structure and biological

activity or mode of action.

Some specific areas that are appropriate include the following.

Design, synthesis, and biological evaluation of novel biologically active compounds,

diagnostic agents, or labeled ligands employed as pharmacological tools.

Molecular modifications of reported series that lead to a significantly improved

understanding of their structure-activity relationships (SAR). Routine extensions of

existing series that do not utilize novel chemical or biological approaches or do not add

significantly to a basic understanding of the SAR of the series will normally not be

considered for publication.

Structural biological studies (X-ray, NMR, etc.) of relevant ligands and targets with the

aim of investigating molecular recognition processes in the action of biologically active

compounds.

Molecular biological studies (e.g., site-directed mutagenesis) of macromolecular targets

that lead to an improved understanding of molecular recognition.

Computational studies that analyze the SAR of compound series of general interest and

lead to experimental studies or analysis of other available chemical and/or biological data

that substantially advance medicinal chemistry knowledge.

Substantially novel computational chemistry methods with demonstrated utility for the

identification, optimization, or target interaction analysis of bioactive molecules.

Effect of molecular structure on the distribution, pharmacokinetics, and metabolic

transformation of biologically active compounds. This may include design, synthesis, and

evaluation of novel types of prodrugs.

Novel methodology with broad application to medicinal chemistry, but only if the

methods have been tested on relevant molecules.

1.2 Manuscript Categories

Manuscripts can be submitted as Articles, Brief Articles, Perspectives, or Drug Annotations.

1.2.1 Articles are definitive, full accounts of significant studies.

1.2.2 Brief Articles are definitive reports whose scope is more limited than the scope of Articles,

but whose format is identical except for length. They are subject to the same editorial appraisal

as Articles and should be of similar scientific quality.

1.2.3 Perspectives are interpretive accounts on subjects of current interest to medicinal chemists.

This series is intended to be a forum for experts to present their perspectives on emerging or

active areas of research that affect the practice of medicinal chemistry. Manuscripts are usually

submitted at the invitation of the Perspectives Editor. However, experts are welcome to contact

the Perspective Editor to ensure that a topic is suitable. Approval is recommended prior to

submission.

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1.2.4 Drug Annotations are reports of drug candidates in phase I, II, and III clinical trials, as well

as new drugs in the market. Drug Annotations manuscripts focus on a single drug and should

provide a description of a candidate molecule (including structure), target(s), mechanism of

action, and rationale for bringing the candidate to clincial trial (for example, first in class or

improvement over previous compounds). Reports on original research are also acceptable.

Manuscripts are usually submitted after an invitation from the Drug Annotations Editors.

However, authors are welcome to contact the Drug Annotations Editors to ensure that a topic is

suitable. Approval is recommended prior to submission.

1.2.5 Viewpoint manuscripts are invited by the Editors. Viewpoint manuscripts are typically

accompanied commentaries to Featured Articles.

1.2.6 Featured Articles are selected by the Editors from accepted Articles, Brief Articles, and

Drug Annotations.

1.3 Prior Publication

Authors should submit only original work that has not been previously published and is not

under consideration for publication elsewhere.

Academic theses, including those on the Web or at a college Web site, are not considered to be

prior publication.

1.4 Patents and Intellectual Property

Authors need to resolve all patent and intellectual property issues. Acceptance and publication

will not be delayed for pending or unresolved issues of this type. Note that Just Accepted

manuscripts (section 3.11) and ASAP manuscripts (section 3.12) are published documents.

1.5 Professional Ethics

Editors, reviewers, and authors are expected to adhere to the American Chemical Society’s

Ethical Guidelines to Publication of Chemical Research. The guidelines are available at

http://pubs.acs.org/page/jmcmar/submission/index.html.

1.5.1 Author Consent. Submitting authors are reminded that consent of all coauthors must be

obtained prior to submission of manuscripts. If an author is removed after submission, the

submitting author must have the removed author consent to the change by e-mail or faxed letter

to the assigned Editor.

1.5.2. Plagiarism. Manuscripts must be original with respect to concept, content, and writing. It

is not appropriate for an author to reuse wording from other publications, including one's own

previous publications, whether or not that publication is cited. Suspected plagiarism should be

reported immediately to the editorial office. Report should specifically indicate the plagiarized

material within the manuscripts.

1.5.3. Use of Human or Animal Subjects. Manuscripts must comply with the ACS Ethical

Guidelines to Publication of Chemical Research: Research involving animals must be performed

in accordance with institutional guidelines as defined by Institutional Animal Care and Use

Committee for U.S. institutions or an equivalent regulatory committee in other countries.

Research studies involving humans must have institutional review board approval. Authors are

requested to identify the institutional or licensing committee that has approved the experiments.

For research involving animals or humans, Editors reserve the right to request additional

information from authors.

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1.6 Issue Frequency

The Journal publishes 24 issues per year on the second and fourth Thursdays of each month.

2 Preparing the Manuscript

2.1 General Considerations

Manuscripts should be kept to a minimum length. Authors should write in clear, concise English,

employing an editing service if necessary. For convenience, ACS has compiled a list of

language-editing companies (http://pubs.acs.org/page/4authors/tools/language_editing.html). The

responsibility for all aspects of manuscript preparation rests with the authors. Extensive changes

or rewriting of the manuscript will not be undertaken by the Editors. Information on a standard

list of abbreviations for ACS Journals is in The ACS Style Guide (2006), available from Oxford

University Press, Order Department, 2001 Evans Road, Cary, NC 27513.

Authors are strongly encouraged to use the templates available on the Journal Web site.

It is best to use the fonts “Times” and “Symbol.” Other fonts, particularly those that do not come

bundled with the system software, may not translate properly. Ensure that all special characters

(e.g., Greek characters, math symbols) are present in the body of the text as characters and not as

graphic representations. Be sure that all characters are correctly represented throughout the

manuscript—e.g., 1 (one) and l (letter l), 0 (zero) and O (letter o).

All text (including the title page, abstract, all sections of the body of the paper, figure captions,

scheme or chart titles, and footnotes and references) and tables should be in one file. Graphics

may be included with the text or uploaded as separate files.

Manuscripts that do not adhere to the guidelines may be returned to authors for correction.

2.1.1 Articles. Articles must be double-spaced including text, references, tables, and legends.

Vertically orient all pages. Use page size 8.5 x 11 inches. This applies to figures, schemes, and

tables as well as text. Manuscripts do not have page limitations but should be kept to a minimum

length. The experimental procedures for all of the steps in the synthesis of target compounds

must be included in the experimental section of the manuscript.

2.1.2 Brief Articles. Manuscripts must not exceed 7 pages of the double-column template

including title page, abstract, text with experimental section, references, tables, illustrations, and

table of contents graphic. The abstract is limited to 75 words. If manuscripts exceed 7 journal

pages at the galley stage, authors will be asked to reduce the length of their manuscripts. To

remain within the page limit, some material may be included in supporting information.

However, the experimental procedures for all of the steps in the synthesis of target compounds

must be included in the experimental section of the manuscript.

2.1.3 Perspectives. Perspectives manuscripts do not have the same headings as other manuscript

types. Author(s) biographies of less than 125 words each should be placed immediately before

the references. Generally, Perspectives are no more than 25 journal pages (100 double-spaced

manuscript pages) and should not contain more than 180 references. Miniperspectives are no

more than 8 journal pages (32 double-spaced manuscript pages) and should not contain more

than 70 references. Page limits for Award Perspectives are flexible, but they should conform to

other requirements stated for Perspectives or Miniperspectvies.

2.1.4 Drug Annotations. Manuscripts should be double-spaced including text, references, tables

and legends. Vertically orient all pages. Use page size 8.5 x 11 inches. This applies to figures,

schemes, and tables as well as text. Limit manuscripts to approximately 40 double-spaced pages

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(10 journal pages), including title page, abstract of 150 words or less, up to 50 references, and

tables, charts, schemes, and figures. In general, manuscripts should include design and

chemistry, known biological targets, in vitro and in vivo biological activity, pharmacological

properties, available toxicity information, and clinical data.

2.1.5 Viewpoint. Manuscripts are limited to 8 double-spaced pages (2 journal pages), including

title page, abstract, references, tables, and illustrations.

2.1.6 Nomenclature. It is the responsibility of the authors to provide correct nomenclature.

Nomenclature should conform to current American usage. It is acceptable to use semisynthetic or

generic names for certain specialized classes of compounds, such as steroids, peptides,

carbohydrates, etc. In such a case, the name should conform to the generally accepted

nomenclature conventions for the compound class. Chemical names for drugs are preferred. If

these are not practical, generic names, or names approved by the U.S. Adopted Names Council

or by the World Health Organization, may be used. Authors may find the following sources

useful for recommended nomenclature:

The ACS Style Guide; Coghill, A. M., Garson, L. R., Eds.; American Chemical Society:

Washington DC, 2006.

Enzyme Nomenclature; Webb, E. C., Ed.; Academic Press: Orlando, 1992.

IUPHAR database of receptors and ion channels (http://www.iuphar-db.org/index.jsp).

2.1.7 Compound Code Numbers. Code numbers assigned to a compound may be used as

follows:

Once in the manuscript title, when placed in parentheses AFTER the chemical or

descriptive name.

Once in the abstract.

Once in the text (includes legends) and once to label a structure. Code numbers in the text

must correspond to structures or, if used only once, the chemical name must be provided

before the parenthesized code number, e.g., “chemical name (JEM-398).” If appearing a

second time in the text, a bold Arabic number must be assigned on first usage, followed

by the parenthesized code number, e.g., “1 (JEM-398).” Subsequently, only the bold

Arabic number may be used. All code numbers in the text must have a citation to a

publication or a patent on first appearance.

Compounds widely employed as research tools and recognized primarily by code numbers may

be designated in the manuscript by code numbers without the above restrictions. Their chemical

name or structure should be provided as above. Editors have the discretion of determining which

code numbers are considered widely employed.

2.1.8 Trademark Names. Trademark names for reagents or drugs must be used only in the

experimental section. Perspectives may use trademark names once in the manuscript. Do not use

trademark or service mark symbols.

2.1.9. Interference Compounds. Active compounds from any source must be examined

for known classes of assay interference compounds and this analysis must be provided in the

General Experimental section. Compounds shown to display misleading assay readouts by a

variety of mechanisms include, but are not limited to, aggregation, redox activity, fluorescence,

protein reactivity, singlet-oxygen quenching, the presence of impurities, membrane disruption,

and their decomposition in assay buffer to form reactive compounds. Many of these compounds

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have been classified as Pan Assay Interference Compounds (PAINS; see Baell & Holloway, J.

Med. Chem. 2010, 53, 2719-2740). Provide firm experimental evidence in at least two different

assays that reported compounds with potential PAINS liability are specifically active and their

apparent activity is not an artifact.

2.2 Manuscript Organization

2.2.1 Title Page. Title: The title of the manuscript should reflect the purposes and findings of the

work in order to provide maximum information in a computerized title search. Minimal use of

nonfunctional words is encouraged. Only commonly employed abbreviations (e.g., DNA, RNA,

ATP) are acceptable. Code numbers for compounds may be used in a manuscript title when

placed in parentheses AFTER the chemical or descriptive name.

Authors' Names and Affiliations: The authors' full first names, middle initials, last names, and

affiliations with addresses at time of work completion should be listed below the title. The name

of the corresponding author should be marked with an asterisk (*).

2.2.2 Abstract. Articles, Brief Articles, Perspectives, and Viewpoints must have an abstract

following the title page. Brief Articles have a strict 75 word limit; for Articles and Perspectives,

150 words are usually adequate; for Viewpoints, 1–3 sentences are adequate. Abstracts should be

presented in a findings-oriented format in which the most important results and conclusions are

summarized. Code numbers may be used once in the abstract.

2.2.3 Introduction. The rationale and objectives of the research should be discussed in this

section. The background material should be brief and relevant to the research described.

2.2.4 Results. This section could include synthetic schemes and tables of biological data. The

discussion of the chemistry and biology should be descriptive.

2.2.5 Discussion and Conclusions. Authors should discuss the analysis of the data together with

the significance of results and conclusions, if an optional conclusions section is not employed.

2.2.6 Experimental Section. Authors should be as concise as possible in experimental

descriptions. General reaction conditions should be given only once. The title of an experiment

should include the chemical name and a bold Arabic identifier number; subsequently, only the

bold Arabic number should be used. Experiments should be listed in numerical order. Molar

equivalents of all reactants and percentage yields of products should be included.

A general introductory section should include general procedures, standard techniques, and

instruments employed (e.g., determination of purity, chromatography, NMR spectra, mass

spectra, names of equipment) in the synthesis and characterization of compounds described

subsequently in this section. Special attention should be called to hazardous reactions or toxic

compounds. Provide analysis for known classes of assay interference compounds.

Abbreviations. Standard abbreviations should be used throughout the experimental section (see

4. Standard Abbreviations and Acronyms). Please note that these are used in ACS Journals

without periods. The preferred forms for some of the more commonly used abbrevations are mp,

bp, ºC, K, min, h, mL, μL, g, mg, μg, cm, mm, nm, mol, mmol, μmol, ppm, TLC, GC, NMR,

UV, and IR. Units are abbreviated in table column heads and when used with numbers, not

otherwise. For further information, refer to The ACS Style Guide (see 2.1 General

Considerations).

2.2.7 Ancillary Information. Include pertinent information in the order listed immediately

before the references.

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Supporting Information Availability. If supporting information has been submitted, include a

statement of the availability using the following format:

Supporting Information. Brief statement in nonsentence format listing the contents of

the material supplied as Supporting Information.

PDB ID Codes: Include the PDB ID codes.

Corresponding Author Information: Provide telephone numbers and email addresses for each of

the designated corresponding authors.

Present/Current Author Addresses: Provide information for authors whose affiliations or

addresses have changed.

Author Contributions: Include statement such as "These authors contributed equally."

Acknowledgment: Authors may acknowledge people, organizations, and financial supporters in

this section.

Abbreviations Used: Provide a list of nonstandard abbreviations and acronyms used in the paper,

e.g., YFP, yellow fluorescent protein. Do not include compound code numbers in this footnote.

It is not necessary to include abbreviations and acronyms from the Standard Abbreviations and

Acronyms list (http://pubs.acs.org/page/jmcmar/submission/authors.html).

2.2.8 References and Notes. Number literature references and notes in one consecutive series by

order of mention in the text. Numbers in the text are non-parenthesized superscripts. The

accuracy of the references is the responsibility of the author. List all authors; do not use et al.

Provide inclusive page numbers. Titles may have capitalization of first word only (excluding, for

example, acronyms and trade names) or standard capitalization as shown below. The chosen

style should be used consistently throughout the references. Double-space the references using

the following format.

For journals: Rich, D. H.; Green, J.; Toth, M. V.; Marshall, G. R.; Kent, S. B. H.

Hydroxyethylamine Analogues of the p17/p24 Substrate Cleavage Site Are Tight-

Binding Inhibitors of HIV Protease. J. Med. Chem. 1990, 33, 1285-1288.

For online early access: Rubner, G.; Bensdorf, K.; Wellner, A.; Kircher, B.; Bergemann,

S.; Ott, I.; Gust, R. Synthesis and Biological Activities of Transition Metal Complexes

Based on Acetylsalicylic Acid as Neo-Anticancer Agents. J. Med. Chem. [Online early

access]. DOI: 10.1021/jm101019j. Published Online: September 21, 2010.

For periodicals published in electronic format only: Author 1; Author 2; Author 3; etc.

Title of Article. Journal Abbreviation [Online] Year, Volume, Article Number or other

identifying information.

For monographs: Casy, A. F.; Parfitt, R. T. Opioid Analgesics; Plenum: New York, 1986.

For edited books: Rall, T. W.; Schleifer, L. S. Drugs Effective in the Therapy of the

Epilepsies. In The Pharmacological Basis of Therapeutics, 7th ed.; Gilman, A. G.,

Goodman, L. S., Rall, T. W., Murad, F., Eds.; Macmillan: New York, 1985; pp 446-472.

List submitted manuscripts as “in press” only if formally accepted for publication. Manuscripts

available on the Web with a DOI number are considered published. For manuscripts not

accepted, use “unpublished results” after the names of authors. Incorporate notes in the correct

numerical sequence with the references. Footnotes are not used.

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2.2.9 Tables. Tabulation of experimental results is encouraged when this leads to more effective

presentation or to more economical use of space. Tables should be numbered consecutively in

order of citation in the text with Arabic numerals. Footnotes in tables should be given italic

lowercase letter designations and cited in the tables as superscripts. The sequence of letters

should proceed by row rather than by column. If a reference is cited in both table and text, insert

a lettered footnote in the table to refer to the numbered reference in the text. Each table must be

provided with a descriptive title that, together with column headings, should make the table self-

explanatory.

Titles and footnotes should be on the same page as the table. Tables may be created using a word

processor’s text mode or table format feature. The table format feature is preferred. Ensure each

data entry is in its own table cell. If the text mode is used, separate columns with a single tab and

use a return at the end of each row. Tables may be inserted in the text where first mentioned or

may be grouped after the references.

2.2.10 Figures, Schemes/Structures, and Charts. The use of illustrations to convey or clarify

information is encouraged. Structures should be produced with the use of a drawing program

such as ChemDraw. Authors using other drawing packages should, in as far as possible, modify

their program’s parameters so that they conform to ChemDraw preferences. Remove all color

from illustrations, except for those you would like published in color. Illustrations may be

inserted into the text where mentioned or may be consolidated at the end of the manuscript. If

consolidated, legends should be grouped on a separate page(s). Include as part of the manuscript

file.

To facilitate the publication process, please submit manuscript graphics using the following

guidelines:

1. The preferred submission procedure is to embed graphic files in a Word document. It

may help to print the manuscript on a laser printer to ensure all artwork is clear and

legible.

2. Additional acceptable file formats are: TIFF, PDF, EPS (vector artwork) or CDX

(ChemDraw file). If submitting individual graphic files in addition to them being

embedded in a Word document, ensure the files are named based on graphic function (i.e.

Scheme 1, Figure 2, Chart 3), not the scientific name. Labeling of all figure parts should

be present and the parts should be assembled into a single graphic.

EPS files: Ensure that all fonts are converted to outlines or embedded in the graphic file.

The document settings should be in RGB mode. NOTE: While EPS files are accepted,

the vector-based graphics will be rasterized for production. Please see below for TIFF

file production resolutions.

3. TIFF files (either embedded in a Word doc or submitted as individual files) should have

the following resolution requirements:

- Black & White line art: 1200 dpi

- Grayscale art (a monochromatic image containing shades of gray): 600 dpi

- Color art (RGB color mode): 300 dpi

The RGB and resolution requirements are essential for producing high-quality

graphics within the published manuscript. Graphics submitted in CMYK or at

lower resolutions may be used; however, the colors may not be consistent and

graphics of poor quality may not be able to be improved.

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Most graphic programs provide an option for changing the resolution when

you are saving the image. Best practice is to save the graphic file at the final

resolution and size using the program used to create the graphic.

4. Graphics should be sized at the final production size when possible. Single column

graphics are preferred and can be sized up to 240 points wide (3.33 in.). Double column

graphics must be sized between 300 and 504 points (4.167 in. and 7 in.). All graphics

have a maximum depth of 660 points (9.167 in.) including the caption (please allow 12

points for each line of caption text).

Consistently sizing letters and labels in graphics throughout your manuscript will help

ensure consistent graphic presentation for publication.

For more information, please visit http://pubs.acs.org/page/jmcmar/submission/authors.html and

http://pubs.acs.org/page/4authors/submission/index.html.

2.2.11 Image Manipulation. According to ACS Ethical Guidelines, images should be free from

misleading manipulation. Images included in an account of research performed or in the data

collection as part of the research require an accurate description of how the images were

generated and produced. Apply digital processing uniformly to images, with both samples and

controls. Cropping must be reported in the figure legend. For gels and blots, use of positive and

negative controls is highly recommended. Avoid high contrast settings to avoid overexposure of

gels and blots. For microscopy, apply color adjustment to entire image and note in the legend.

When necessary, authors should include a section on equipment and settings in supporting

information to describe all image acquisition tools, techniques and settings, and software used.

All final images must have resolutions of 300 dpi or higher. Authors should retain unprocessed

data in the event that the Editors request them. Unprocessed data can also be part of the

supporting information.

2.2.12 Table of Contents Graphic. A graphic entry for the table of contents (TOC) must be

supplied as the last page of the manuscript and labeled “Table of Contents graphic.” This small

graphic should capture the reader's attention and, in conjunction with the manuscript title, should

give the reader an idea of the key target compounds or series discussed in the paper. The TOC

graphic will also appear in the abstract of the published PDF file.

• A chemical structure should be clearly depicted.

• The TOC graphic should be entirely original work created by one of the coauthors and should

not be a duplicate of a graphic appearing elsewhere in the manuscript.

• The TOC graphic should be no wider than 21 cm and no taller than 5.5 cm.

• Code numbers should not be used in the TOC graphic.

For additional information see the ACS Publications Guidelines for Table of Contents/Abstract

Graphics. For resolution/quality requirements see Figures, Schemes/Structures, and Charts.

2.2.13 Supporting Information. Authors are encouraged to make use of this resource when

manuscripts contain extensive tabulations of data that are of interest only to those readers who

may need more complete data.

The first page of the supporting information file should contain the title of the manuscript, the

names of all authors, and a table of contents; label this page “Supporting Information”. The

pages must be consecutively numbered S1 (the title page), S2, etc. Figure captions, titles to

tables, and other identifying captions should appear on the same page as the figures or tables.

Supporting information may be single-spaced. Generally, if one has difficulty reading the

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material as submitted, it is unacceptable. Refer to The ACS Style Guide (see 2.1 General

Considerations) for more specific information.

Supporting information must be submitted at the same time as the manuscript and uploaded

separately to the ACS Paragon Plus Environment. A list of acceptable file types is available on

the Web. All supporting information files of the same type should be prepared as a single file

(rather than submitting a series of files containing individual images or structures). For example,

all supporting information available as PDF files should be contained in one PDF file. Author-

created file names will be automatically replaced with standardized file names generated at the

time of publication.

DO NOT UPLOAD FIGURES AND TABLES THAT ARE TO BE PUBLISHED IN THE

MANUSCRIPT INTO THE SUPPORTING INFORMATION FILE.

2.2.14 Molecular Formula Strings. Authors are encouraged to submit SMILES string

computer-readable identifiers of molecules discussed in the manuscript along with the associated

biochemical and biological data. Submission of molecular formula strings and associated data

enables enhanced quality control at review and can increase an article's discoverability and

citability. Complete submission instructions are available at

http://pubs.acs.org/page/jmcmar/submission/jmcmar_mfstrings.html.

2.3 Specialized Data

2.3.1 Biological Data. Quantitative biological data are required for all tested compounds.

Biological test methods must be referenced or described in sufficient detail to permit the

experiments to be repeated by others. Detailed descriptions of biological methods should be

placed in the experimental section. Standard compounds or established drugs should be tested in

the same system for comparison. Data may be presented as numerical expressions or in graphical

form; biological data for extensive series of compounds should be presented in tabular form.

Tables consisting primarily of negative data will not usually be accepted; however, for purposes

of documentation they may be submitted as supporting information.

Active compounds obtained from combinatorial syntheses should be resynthesized and retested

to verify that the biology conforms to the initial observation.

Statistical limits (statistical significance) for the biological data are usually required. If statistical

limits cannot be provided, the number of determinations and some indication of the variability

and reliability of the results should be given. References to statistical methods of calculation

should be included. Doses and concentrations should be expressed as molar quantities (e.g.,

mol/kg, μmol/kg, M, mM). The routes of administration of test compounds and vehicles used

should be indicated, and any salt forms used (hydrochlorides, sulfates, etc.) should be noted. The

physical state of the compound dosed (crystalline, amorphous; solution, suspension) and the

formulation for dosing (micronized, jet-milled, nanoparticles) should be indicated. For those

compounds found to be inactive, the highest concentration (in vitro) or dose level (in vivo) tested

should be indicated. See section on Statistical Criteria for more detailed requirements.

Cytotoxicity mean graphs from the National Cancer Institute (NCI) should appear in Supporting

Information and not in the main body of the manuscript. Numerical data derived from a limited

number of cell lines may be tabulated in the text of the manuscript.

2.3.2 Purity of Tested Compounds.

Methods: All scientifically established methods (e.g., HPLC, combustion analysis, absolute

quantitative 1H NMR (qHNMR) following the established Journal protocol or equivalent

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qHNMR methods) of establishing purity are acceptable. If the target compounds are solvated, the

quantity of solvent should be included in the compound formulas. No documentation is required

with the exception of qHNMR (see Purity by Absolute qNMR instructions).

Purity Percentage: All tested compounds, whether synthesized or purchased, should possess a

purity of at least 95%. Target compounds must have a purity of at least 95%. In exceptional

cases, authors can request a waiver when compounds are less than 95% pure. For solids, the

melting point or melting point range should be reported as an indicator of purity.

Statements: Include the specific analytical method used to determine purity in the general part of

the experimental section together with a statement confirming 95% purity. If the purity of a

particular compound is less than 95%, specify the percentage of purity at the end of the

description of its synthesis in the experimental section. For qHNMR experiments, additional

documentation is required.

Cover Letter: Specify the method employed for establishing purity and percentage of purity in

the cover letter. Waivers for compounds of less than 95% purity should be requested in the cover

letter.

2.3.3 Confirmation of Structure. Adequate evidence to establish structural identity must

accompany all new compounds that appear in the experimental section of Articles and Brief

Articles. Sufficient spectral data should be presented in the experimental section to allow for the

identification of the same compound by comparison. Generally, a listing of 1H or

13C NMR

peaks is sufficient. However, when the NMR data are used as a basis of structural identification,

the peaks must be assigned. See NMR Guidelines for ACS Journals.

List only infrared absorptions that are diagnostic for key functional groups. If a series contains

very closely related compounds, it may be appropriate merely to list the spectral data for a single

representative member when they share a common major structural component that has identical

or very similar spectral features. HRMS data may be supplied as an additional criterion of

compound identity. For the first member of a new class of oligomers containing up to 10

residues, 1H NMR (300-500 MHz) and HRMS are a requirement.

Specific optical rotations should be reported for isolated natural products, enantiopure

compounds, and enantioenriched isomer mixtures when sufficient sample is available. Specific

rotations based on the equation [α] = (100α)/(lc) should be reported as unitless numbers as in the

following example: [α]20

D 25 (c 1.9, CHCl3), where the concentration c is in g/l00 mL and the

path length l is in decimeters. The units of the specific rotation, (deg*mL)/(g*dm), are implicit

and are not included with the reported value.

2.3.4 Combinatorial Chemistry. When combinatorial chemistry has been employed to generate

molecules which become prototypes for a subsequent focused SAR investigation, the lead

compounds and any other compounds that are key to the analysis and interpretation of the SAR

of the focused series must conform to the appropriate criteria for purity and structural identity

required by this Journal. However, the combinatorial chemistry methodology, screening data,

and preliminary SAR which led to the generation of the lead molecule(s) may be reported as

supporting information without confirmation of structure or demonstration of purity. These data

may be briefly summarized in the main manuscript when they clarify the SAR discussion of the

focused series.

2.3.5 Computational Chemistry.

2.3.5.1 Manuscript Categories. When computational chemistry is a major component of a study,

manuscripts must fall into one or more of the following categories:

12

(A) Practical applications of existing computational methods combined with original

experimental data. Manuscripts that report prospective computational design, synthesis, and

experimental evaluation of new chemical entities are highly encouraged.

Applications of existing computational methods are not considered without original experimental

data that assess the computational predictions. QSAR modeling is acceptable only if a significant

number of new compounds is predicted, prepared, and tested. Avoid overinterpretation of

computational predictions and conclusions drawn from molecular models as if they represent

experimental data.

(B) Substantially novel methods along with evidence for utility in medicinal chemistry with

significant potential for advancing the field.

Clearly describe computational methods manuscripts to be accessible to a general medicinal

chemistry audience and clarify the relevance of the new method to medicinal chemistry. Present

sufficient information to allow the method to be reproduced and tested in other laboratories.

(C) Statistical analysis or data mining of publicly available databases or data sets that provide

unexpected or provocative insights into the advancement of topical medicinal chemistry

problems.

Such investigations must be based upon large data sets. Small series of compounds whose

properties are reinvestigated using computational methods do not qualify for this category.

2.3.5.2 Proprietary Data. Normally, the use of proprietary data for computational modeling or

analysis is not acceptable because it is inconsistent with the ACS Ethical Guidelines. All

experimental data and molecular structures used to generate and/or validate computational

models must be reported in the paper, reported as supporting information, or readily available

without infringements or restrictions. The Editors may choose to waive the data deposition

requirement for proprietary data in a rare case where studies based on very large corporate data

sets provide compelling insight unobtainable otherwise.

2.3.5.3 Virtual Screening Studies. In order to validate virtual screening hits obtained from any

source, provide proof of dose-response behavior, confirmation of IC50 or Ki values, and controls

for nonspecific or artificial inhibition (i.e., proof of reversibility, detergent controls). Submit

structure confirmation (1H NMR and MS; see section 2.3.3) for active compounds.

For virtual screens that produce compound rankings, provide as supporting information the total

number of compounds that were screened and the ranks of identified hits before application of

any further manual or other subjective selection steps.

Complex virtual screening protocols are not validated per se by identifying a few active

compounds. Evidence must be provided that much simpler approaches would not have yielded

comparable results (e.g., 2D similarity or substructure searching). Experimental findings must be

significant. For example, identifying weakly potent ATP-site directed protein kinase inhibitors

through virtual screening is no longer considered a significant advance due to the availability of

many known potent inhibitors acting by this mechanism.

2.3.5.4 Retrospective Use of Computational Methods. Manuscripts that contain experimental

studies with a retrospective computational component will be considered only under the

following conditions:

(a) Computational work must lead to a clearly stated message, either an improved understanding

of the experimental work or a well-defined experimentally testable hypothesis.

(b) Clearly distinguish models and hypothetical statements from experimental observations both

13

in the text and in figure captions.

(c) Describe computational methods in sufficient detail for the reader to reproduce the results.

(d) Computational methods must be thoughtfully selected. Explain why the applied method is an

appropriate choice and was chosen over similar existing methods. Calculation results, in

particular those of automated modeling software, must be critically examined.

(e) Draw conclusions from modeling with an appropriate amount of caution in light of

assumptions made and within the accuracy limitations of the applied computational methods.

The overall amount of space (text and figures) devoted to retrospective computational work must

be proportionate to its significance.

2.3.5.5 Predicted Compound Binding Modes. The prediction of compound binding modes by

docking is a frequent computational application submitted to the Journal in combination with

experimental data. Models derived by minor modifications of known X-ray structures are often

reliable, whereas binding modes suggested on the basis of a protein homology model are usually

speculative. To be considered for publication in the Journal, all binding mode predictions must

be well founded. In the absence of supporting structural information, demonstrate that putative

binding modes are consistent with structure–activity relationships for a series of analogues.

QSAR, pseudo-receptor, or machine learning models that are occasionally applied

retrospectively to analyze biological activities observed in the context of experimental SAR

studies are acceptable only when used in a predictive fashion or used to illustrate a point of

central relevance for a manuscript.

2.3.5.6 Computational Data Analysis. The Journal encourages the submission of manuscripts

presenting analyses of publicly available databases or data sets that provide unexpected or

provocative insights into topical problems and advance medicinal chemistry knowledge.

Investigations must be based upon large data sets rather than small series of compounds.

Benchmark investigations, such as comparisons of virtual screening algorithms, are considered

only if they provide particularly clear and generally relevant conclusions that set new standards

in the field. General relevance must be clearly stated and put into scientific context.

2.3.6 QSAR/QSPR and Proprietary Data. The following are general requirements for

manuscripts reporting work done in this area:

(1) Authors should explicitly state in the abstract, introduction, and/or results sections of the

paper what is novel about the quantitative structure–activity relationships/quantitative structure–

property relationships (QSAR/QSPR) study being reported. In this respect, "novel" must be

presented with respect to methodology/theory and/or the findings from the system(s) studied.

(2) If a new method/theory is being reported, it should be compared and “validated” against at

least one other common data set of reasonable size for which a published study exists using at

least one other method/approach and preferably a method/approach that has been widely used in

the field.

(3) All data and molecular structures used to carry out a QSAR/QSPR study are to be reported in

the paper and/or in its supporting information or should be readily available without

infringements or restrictions. The use of proprietary data is generally not acceptable.

(4) Standard QSAR/QSPR studies are considered only if the predictions are experimentally

tested and if the experimental data are novel and significant. Only QSAR/QSPR analyses that

provide new insights into the activity are encouraged.

14

Some guidelines to assist prospective Journal authors of manuscripts in the field of QSAR/QSPR

that report novel methods are as follows:

(i) 3D-QSAR studies that overlap with, and enhance, structure-based design (SBD) methods are

encouraged. QSAR models that lead to subsequently validated experimental findings are

encouraged.

(ii) Papers reporting new QSAR/QSPR methods and approaches for facilitating a mechanistic

understanding of ADMET properties, and/or for reliable ADMET screening, are welcomed.

(iii) New QSAR/ QSPR methods that interface with chem- and bio-informatics methods and/or

with data-mining techniques are encouraged.

(iv) QSAR/QSPR approaches for virtual screening must demonstrate distinct advantages or

advances over current virtual screening schemes. For methods falling into categories (1)-(3), the

same acceptance criteria apply as for any manuscript describing new computational methods

according to 2.3.5.

Specifically discouraged are (a) QSAR and QSPR modeling for data sets that have already been

extensively modeled, (b) model development featuring high ratios of descriptors to data points,

and (c) reports of new descriptors without clear evidence for their superiority in QSAR/QSPR

modeling to existing, commonly used alternatives.

2.3.7 Statistical Criteria. Appropriate statistical assessment is equally important for

experimental and computational studies in medicinal chemistry. Reported results generally

require statistical validation. Statistical analyses of compound data are also frequently presented,

which must adhere to acceptable statistical and scientific standards. Specifically:

(1) A clear and comprehensive description of experimental data or computed data underlying the

analysis is required.

(2) Statistical methods used must be clearly identified. Non-standard statistical methods should

be described in sufficient detail or precisely referenced.

(3) Underlying assumptions of statistical methods should be specified. For example, many

statistical tests assume the presence of normal data distributions, which is often an approximation

in practice.

(4) Depending on the type of experiments reported, either confidence limits must be provided or

a statistical significance analysis performed. For example, assay curves must contain errors bars

derived from multiple measurements.

(5) For regression curves, their uncertainty must be assessed by plotting the original data along

the curve or by establishing experimental or calculation confidence limits.

(6) If average values are reported from computational analysis, their variance must be

documented. This can be accomplished by providing the number of times calculations have been

repeated, mean values, and standard deviations (or standard errors). Alternatively, median values

and percentile ranges can be provided. Data might also be summarized in scatter plots or box

plots.

(7) Reporting averages of data assigned to pre-defined value ranges and ‘averages of average

values’ must be avoided.

2.3.8 Software. Software used as a part of computer-aided drug design (e.g., molecular modeling

or QSAR) should be readily available from reliable sources, and the authors should specify

where the software can be obtained. When conformational calculations are included in such

15

papers, the parameters employed for the relevant potential functions should be given. All details

needed to reproduce the numbers in the manuscript should be indicated in the paper or as

supporting information. This includes coordinates of hypothetical computer-generated receptor

models. Authors should refer to J. Med. Chem. 1988, 31, 2230–2234 for publication guidelines.

2.3.9 Structural Data. For papers describing structures of biological macromolecules, the

atomic coordinates and the related experimental data (structure factor amplitudes/intensities

and/or NMR restraints) must be deposited at a member site of the Worldwide Protein Data Bank

(http://www.wwpdb.org): RCSB PDB (http://www.pdb.org), Protein Databank in Europe

(PDBe) (http://www.ebi.ac.uk/pdbe/docs/References.html), PDBj (http://www.pdbj.org), or

BMRB (http://www.bmrb.wisc.edu). The PDB ID must appear before the references (see section

2.2.7). Authors must agree to release the atomic coordinates and experimental data when the

associated article is published. Questions related to deposits should be sent to info@wwpdb.org.

Papers that utilize coordinates of molecules already in the database should specify the PDB ID as

a reference.

For X-ray diffraction of structures of small molecules with anisotropically refined atoms, a figure

displaying the thermal ellipsoids should ordinarily be presented; a spherical-atom representation

may be substituted if necessary for clarity. If a spherical atom view is chosen for the manuscript,

a thermal ellipsoid figure should be included in the supporting information. In cases where

intermolecular interactions are relevant to the discussion, a view of the unit cell may be included.

Articles should list for each structure the formula, formula weight, crystal system, space group,

unit cell parameters, temperature of data collection, and values of Z, R, and GOF in the

experimental section. Tables of atom coordinates and thermal parameters will not be printed. CIF

files must be deposited with Cambridge Crystallographic Data Centre (CCDC).

2.3.10 Compound Characterization Checklist. When manuscripts report the synthesis of

compounds, submission of a completed Compound Characterization Checklist (CCC) is

recommended but not required. The CCC form (accessed via

http://pubs.acs.org/page/jmcmar/submission/authors.html) can be completed on-screen and saved

for uploading with the submission of the manuscript (Supporting Information for Review Only).

The CCC will be provided to reviewers to help them assess the overall thoroughness of the

characterization of synthesized compounds.

3 Submitting the Manuscript

3.1 Paragon Plus Web Site

Manuscripts must be submitted via the ACS Paragon Plus Environment

(http://paragonplus.acs.org/login). Complete instructions and an overview of the electronic

online (Web) submission process are available through the secure ACS Paragon Plus Web site.

Authors will view the PDF version of their manuscripts prior to formal submission to the Editor.

In order to use Web submission, authors must be able to provide electronic versions of text and

graphics. Supporting information should also be submitted electronically via the Web site (as a

separate document). Instructions on supported platforms and word processing packages are

available at the submission site.

The Web submission site employs state-of-the-art security mechanisms to ensure privacy for all

electronically submitted manuscripts. These same security mechanisms are also used throughout

the peer review process, permitting access to only those reviewers who are assigned to a

particular manuscript. Authors must also submit all revisions of manuscripts via the ACS

Paragon Plus Environment. Authors should review the Journal’s most recent Guidelines for

16

Authors on the Web prior to submission of a manuscript. Close attention to all the required

details discussed in Guidelines for Authors will expedite review and reduce the time to

publication.

3.2 Cover Letter

The cover letter should include the manuscript type and corresponding author’s name, e-mail

address, and telephone and fax numbers. Include special instructions (e.g., publish back-to-back

with companion paper). Specify the method employed in determining purity (see 2.3.2 Purity of

Tested Compounds) and that the purity requirements have been met.

3.3 Conflict of Interest Disclosure

A statement describing any financial conflicts of interest or lack thereof is published with each

manuscript. During the submission process, the corresponding author must provide this

statement on behalf of all authors of the manuscript. The statement should describe all potential

sources of bias, including affiliations, funding sources, and financial or management

relationships, that may constitute conflicts of interest (please see the ACS Ethical Guidelines).

The statement will be published in the final article. If no conflict of interest is declared, the

following statement will be published in the article: “The authors declare no competing financial

interest.”

3.4 Journal Publishing Agreement

A properly completed and signed Journal Publishing Agreement must be submitted for each

manuscript. ACS Paragon Plus provides an electronic version of the Agreement that will be

available on the My Authoring Activity tab of the corresponding author's home page once the

manuscript has been assigned to an Editor. A PDF version of the Agreement is also available, but

authors are strongly encouraged to use the electronic Journal Publishing Agreement. If the

PDF version is used, all pages of the signed PDF Agreement must be submitted. If the

corresponding author cannot or should not complete either the electronic or PDF version for any

reason, another author should complete and sign the PDF version of the form. Forms and

complete instructions are available at http://pubs.acs.org/page/copyright/journals/index.html.

3.5 Author List

During manuscript submission, the submitting author must provide contact information (full

name, email address, institutional affiliation and mailing address) for all of the co-authors.

Because all of the author names are automatically imported into the electronic Journal Publishing

Agreement, the names must be entered into ACS Paragon Plus in the same sequence as they

appear on the first page of the manuscript. (Note that co-authors are not required to register in

ACS Paragon Plus.) The author who submits the manuscript for publication accepts the

responsibility of notifying all co-authors that the manuscript is being submitted. Deletion of an

author after the manuscript has been submitted requires a confirming letter to the assigned editor

from the author whose name is being deleted. For more information on ethical responsibilities of

authors, see the Ethical Guidelines to Publication of Chemical Research.

3.6 Funding Sources

When submitting a manuscript to the Journal via ACS Paragon Plus, the submitting author is

asked to identify the funding sources for the work presented in the manuscript. Identifying

funding sources is optional during submission of an original manuscript. Funding source

information is required when a revised manuscript is submitted.

17

3.7 ORCID

All authors are encouraged to register for an ORCID iD, a unique researcher identifier. With this

standard identifier, you can create a profile of your research activities to distinguish yourself

from other researchers with similar names and make it easier for your colleagues to find your

publications. Learn more at http://www.orcid.org.

Authors and reviewers can add their ORCID iD to, or register for an ORCID iD from, their

account in ACS Paragon Plus. Submitting authors have the option to provide existing ORCID

iDs for coauthors during submission, but they cannot create new ORCID iDs for coauthors.

3.8 Revision

Articles, Brief Articles, Perspectives, and Drug Annotations revisions must be submitted within

30 days of a minor revision request and 60 days of a major revision request.

3.9 Proofs

The corresponding author of an accepted manuscript will receive e-mail notification and

complete instructions when page proofs are available for review via a secure Web site. Authors

will access the secure site through ACS ChemWorx and will need an ACS ID. To obtain an ACS

ID or to reset your password, go to www.acschemworx.org.

Routine rephrasing of sentences or additions are not permitted at the page proof stage.

Alterations should be restricted to serious changes in interpretation or corrections of data.

Extensive or important changes on page proofs, including changes to the list of authors or major

changes to the title, are subject to editorial review.

It is the responsibility of the corresponding author to ensure that all authors listed on the

manuscript agree with the changes made on the proofs. Galley proofs should be returned within

48 hours of receipt in order to ensure timely publication of the manuscript. Only the

corresponding author should submit one set of galley corrections to the American Chemical

Society.

3.10 ACS Policies for E-prints and Reprints

Under the ACS Articles on Request policy, the Society will provide (free of charge) to all

contributing authors a unique URL within the ACS Web site that they may e-mail to colleagues

or post on external Web sites. These author-directed links are designed to facilitate distribution

of an author’s published work to interested colleagues in lieu of direct distribution of the PDF

file by the author. The ACS Articles on Request policy allows 50 downloads within the first year

after Web publication and unlimited access via the same author-directed links 12 months after

Web publication.

ACS AuthorChoice options establish fee-based mechanisms for authors or their research funding

agencies to sponsor the open availability of final published articles on the Web. ACS

AuthorChoice offers authors a wide range of open access license options, such as Creative

Commons licenses and provisions for immediate or 12-month embargoed open access, and

includes ACS Certified Deposit. Authors will find useful information about compliance with

open access policies available here and FAQs here. Corresponding authors who published with

ACS during 2014 may have access to ACS Author Rewards, a $60M stimulus program ACS

provided to help authors transition to new open access publishing models.

Authors must sign the Journals Publishing Agreement. Forms and complete instructions are

available here. After acceptance, authors will be presented with the opportunity to purchase an

18

ACS AuthorChoice option, and authors who do so will be presented with the appropriate license

at that time. For a review of all license options available, see here. For questions or further

assistance with ACS AuthorChoice, please contact support@services.acs.org.

For Paper Reprints: When the corresponding author is e-mailed the notification for the proof of

the paper, the author will receive a link to a Web site where the author may order reprints.

Ordering may also be done by calling Cierant Corporation, 866-305-0111, from 9 AM to 5 PM

EST. Reprints will be shipped within two weeks after the issue publication date. Neither the

Editors nor the Washington ACS Office keeps a supply of reprints; requests for single copies of

papers should be addressed to the corresponding author of the paper concerned.

3.11 Just Accepted Manuscripts

Just Accepted manuscripts are peer-reviewed, accepted manuscripts that are published on the

ACS Publications Web site prior to technical editing, formatting for publication, and author

proofing—usually within 30 minutes to 24 hours of acceptance by the editorial office. Authors

should take this schedule into account when planning intellectual and patent activities related to a

manuscript. During the manuscript submission process, authors can choose to have their

manuscript published online as a Just Accepted manuscript. To ensure rapid delivery of the

accepted manuscript to the Web, authors must adhere carefully to all requirements in the

Journal’s Guidelines for Authors. For further information, please refer to the Just Accepted FAQ,

at http://services.acs.org/pubshelp/passthru.cgi?action=kb&item=244. Note that publishing a

manuscript as Just Accepted is not a means by which to comply with the NIH Public Access

Mandate.

3.12 Post Acceptance and ASAP Publication

Correspondence regarding accepted papers, proofs, and reprints should be directed to Journal

Publications, American Chemical Society, 2540 Olentangy River Road, P.O. Box 3330,

Columbus, OH 43210; 614-447-3665; fax, 614-447-3745; acsproof@acs.org.

Accepted manuscripts will be published on the “Articles ASAP” page on the Journal Web site as

soon as page proofs are corrected and all author concerns are resolved. Publication on the Web

usually occurs within 4 working days of receipt of page proof corrections, and this can be

anywhere from 3 to 6 weeks in advance of the cover date of the issue. Manuscripts assigned to a

special issue often remain published ASAP for several months. Unless the paper has already

been published as a Just Accepted manuscript, authors should take this schedule into account

when planning intellectual and patent activities related to a manuscript. The first date on which

an accepted paper is published on the Web (be it Just Accepted, ASAP, or issue) is recorded in

the Web version of the manuscript and on the first page of the PDF version.

3.13 Corrections

Additions and Corrections may be used to address important issues or correct errors and

omissions of consequence that arise after publication of an article. Additions and Corrections

may be requested by the author(s) or initiated by the Editor after discussions with the

corresponding author. Readers who detect errors of consequence in the work of others should

contact the corresponding author of that work. All Additions and Corrections are subject to

approval by the Editor, and minor corrections and additions will not be published. Additions and

Corrections from authors should be submitted via the ACS Paragon Plus environment by the

corresponding author for publication in the “Addition/Correction” section of the Journal. The

corresponding author should obtain approval from all of the article coauthors prior to submitting

an Addition and Correction, or provide evidence that such approval has been solicited. The

19

Addition and Correction should include the original article title and author list, citation including

DOI, and details of the correction. For proper formatting, see examples in a current issue of the

Journal. Please follow the submission instructions on the Information for Authors page.

3.14 Retractions

Articles may be retracted for scientific or ethical reasons. Articles that contain seriously flawed

or erroneous data such that their findings and conclusions cannot be relied upon may be retracted

in order to correct the scientific record. Retractions may be requested by the article author(s) or

by the journal Editor(s) but are ultimately published at the discretion of the Editor. When an

article is retracted, a notice of Retraction will be published containing information about the

original article title, author list, and the reason for the Retraction. Retracted articles will be

accompanied by the related Retraction notice and will be marked as “Retracted”. The originally

published article will remain on the Web except in extraordinary circumstances (e.g., where

deemed legally necessary, or if the availability of the published content poses public health

risks). The American Chemical Society follows guidance from the Committee on Publication

Ethics (COPE) when considering retractions; for more information see

http://publicationethics.org/.

4. Standard Abbreviations and Acronyms

α observed optical rotation in degrees

[α] specific rotation [expressed without

units; the units, (deg⋅mL)/(g⋅dm),

are understood]

δ chemical shift in parts per million

downfield from tetramethylsilane

μ micro

Å angstrom(s)

°C degrees Celsius

2-D two-dimensional (also 2D)

3-D three-dimensional (also 3D)

5HT 5-hydroxytryptamine (serotonin)

9-BBN 9-borabicyclo[3.3.1]nonyl

9-BBN–H 9-borabicyclo[3.3.1]nonane

A amyloid -protein

aa amino acid

AA arachidonic acid

Ac acetyl

Acac acetylacetonate

AcCh; ACh acetylcholine

AcChE; AChE acetylcholine esterase

ACE angiotensin-converting enzyme

ACP acyl carrier protein

ACTH adrenocorticotropic hormone

AD Alzheimer’s disease

ADH antidiuretic hormone

ADME absorption, distribution,

metabolism and excretion

ADMET absorption, distribution,

metabolism, excretion, and

toxicity

ADP adenosine 5'-diphosphate

ADR adverse drug reaction

AE adverse event

AIBN 2,2'-azobisisobutyronitrile

AIDS acquired immune deficiency

syndrome

ALK anaplastic lymphoma kinase

ALS amyotrophic lateral sclerosis

AM1 Austin model 1

AMI acute myocardial infarction

AML acute myelogenous leukemia

AMP adenosine 5'-monophosphate;

adenosine 5'-phosphate

AMPA 2-amino-3-(3-hydroxy-5-methyl-4-

isoxazolyl)propionic acid

Anal. combustion elemental analysis

anhyd; anh anhydrous

ANP atrial natriuretic peptide

antilog antilogarithm

AO atomic orbital

API active pharmaceutical ingredient

ApoB Apolipoprotein B

ApoE Apolipoprotein E

APP amyloid- precursor protein

aq aqueous

Ar aryl

ARB angiotensin receptor blocker

ARDS adult respiratory distress syndrome

atm atmosphere(s)

ASO antisense oligonucleotide

ATP adenosine 5'-triphosphate

ATPase adenosine triphosphatase

AUC area under the curve

20

b.i.d. twice a day

B3LYP 3-parameter hybrid Becke

exchange/ Lee–Yang–Parr

correlation functional

BACE beta-site amyloid precursor protein

cleaving enzyme

BACE-1 beta-secretase

BBB blood-brain barrier

BChE; BuChE butyrylcholinesterase

Bcl-xL B-cell lymphoma-extra large

BMI body mass index

Bn benzyl

BOC, boc tert-butoxycarbonyl

bp boiling point; base pair

BPH Benign Prostatic Hypertrophy

BRCA1 breast cancer gene 1

BSA bovine serum albumin

Bu, n-Bu normal (primary) butyl

BUN blood urea nitrogen

Bz benzoyl (not benzyl)

ca. circa, about [used before an

approximate date or figure (ca.

1960)]

CADD computer-assisted drug design

calcd calculated

cAMP 3',5'-cyclic adenosine

monophosphate

CAN ceric ammonium nitrate

CASPT2 complete active space with second-

order perturbation theory

CASSCF complete active space self-

consistent field

cat catalytic

CB cannabinoid

CBC complete blood count

CBZ, Cbz benzyloxycarbonyl (preferred over

the abbreviation Z)

CC coupled cluster

CCK cholecystokinin

CD circular dichroism

CDC center for disease control

CDER Center for Drug Evaluation and

Research, FDA

CDK cyclin-dependent kinase

cDNA complementary deoxyribonucleic

acid

CETP cholesteryl ester transfer protein

cGLP current good laboratory practices

cGMP current good manufacturing

practice; 3,5'-cyclic guanosine

monophosphate

CGRP calcitonin gene-related peptide

CHF congestive heart failure

CHK1 checkpoint kinase 1

CHK2 checkpoint kinase 2

CHMP Committee for Medicinal Products

for Human Use

Ci curie

CI chemical ionization; configuration

interaction

CIDNP chemically induced dynamic

nuclear polarization

CIF crystallographic information file

CKD chronic kidney disease

cLopP calculated logP

cm centimeter(s)

cm–1

wavenumber(s)

CML chronic myelogenous leukemia

CMV cytomegalovirus

CNS central nervous system

CoA coenzyme A

cod 1,5-cyclooctadiene

CoMFA comparative molecular field

analysis

compd compound

CoMSIA computational molecular similarity

index analysis

concd concentrated

conc; concn concentration

COPD chronic obstructive pulmonary

disease

CoQ coenzyme Q10

COSY correlation spectroscopy

COX cyclooxygenase

Cp cyclopentadienyl

CRH corticotrophin-releasing hormone

CRP C-reactive protein

CSF cerebrospinal fluid

CV cyclic voltammetry

Cy cyclohexyl

CYP cytochrome P

d day(s); doublet (spectral); deci

d density

DA dopamine

DABCO 1,4-diazabicyclo[2.2.2]octane

DART developmental and reproductive

toxicology

DAT dopamine transporter

DBN 1,5-diazabicyclo[4.3.0]non-5-ene

DBP diastolic blood pressure

DBU 1,8-diazabicyclo[5.4.0]undec-7-ene

DCC N,N'-dicyclohexylcarbodiimide

DCE 1,2-dichloroethane

DCM dichloromethane

DDI drug-drug interaction

DDQ 2,3-dichloro-5,6-dicyano-1,4-

benzoquinone

DDT 1,1,1-trichloro-2,2-bis(p-

chlorophenyl)ethane

de diastereomeric excess

DEAD diethyl azodicarboxylate

dec decomposition

DEPT distortionless enhancement by

polarization transfer

21

DFT density functional theory

DIBALH diisobutylaluminum hydride

DIO diet induced obesity

DLT dose limiting toxicity

DMA dimethylacetamide

DMAP 4-(N,N-dimethylamino)pyridine

DMDO dimethyldioxirane

DME 1,2-dimethoxyethane

DMF dimethylformamide

DMPK drug metabolism and

pharmacokinetics

DMPU 1,3-dimethyl-3,4,5,6-tetrahydro-

2(1H)-pyrimidinone

DMSO dimethyl sulfoxide

DMT 4,4'-dimethoxytrityl (4,4'-

dimethoxyltriphenylmethyl)

DNA deoxyribonucleic acid

Dopa 3-(3,4-dihydroxyphenyl)alanine

(also DOPA)

DTT dithiothreitol

e.g. for example (exempli gratia)

E1 unimolecular elimination

E2 bimolecular elimination

EC50 half maximal effective

concentration

ECG electrocardiogram

ED50 dose effective in 50% of test

subjects

EDTA ethylenediaminetetraacetic acid

ee enantiomeric excess

EEG electroencephalogram

EGF epidermal growth factor

EGFR epidermal growth factor receptor

EI electron impact

EKG electrocardiogram

ELISA enzyme-linked immunosorbent

assay

EPR electron paramagnetic resonance

eq equation

equiv equivalent

er enantiomer ratio

ERK extracellular regulated kinase

ESI electrospray ionization

ESR electron spin resonance

Et ethyl

et al. and others

etc. and so forth

F% % oral bioavailability

FAAH fatty acid amide hydrolase

FAB fast atom bombardment

FAD flavin adenine dinuleotide

FaSSIF fasted state simulated intestinal

fluid

FBDD fragment-based drug discovery

FD field desorption

FDA Food and Drug Administration

FeSSIF fed state simulated intestinal fluid

FGF fibroblast growth factor

FID flame ionization detector; free

induction decay

Fmoc 9-fluorenylmethoxycarbonyl

FRET Förster resonance energy transfer

FSH follicle-stimulating hormone

FT Fourier transform

g gram(s); prefix to NMR

abbreviation denoting gradient-

selected (e.g. gCOSY, gHMQC)

GABA -aminobutyric acid

GC gas chromatography

GDP guanosine 5'-diphosphate

GERD gastroesophogeal reflux disease

GFP green fluorescent protein

GFR glomerular filtration rate

GI gastrointestinal

GLP-1 glucagon like peptide-1

GlyR glycine receptor

GMP guanosine 5'-monophosphate;

guanosine 5'-phosphate

GnRH gonadotropin-releasing hormone

GPCR G-protein coupled receptor

GFR growth factor receptor

GST glutathione S-transferase

GTP guanosine 5'-triphosphate

h hour(s); human

HBA hydrogen bond acceptors

HBD hydrogen bond donors

HBV hepatitis B virus

HCS high-content screening

HCV hepatitis C virus

HDAC histone deacetylase

hERG human Ether-a-go-go-Related Gene

HDL-C high-density lipoprotein cholesterol

HEK human embryonic kidney

HF Hartree–Fock

HGH human growth hormone

HIV human immunodeficiency virus

HMBC heteronuclear multiple bond

correlation

HMPA hexamethylphosphoric triamide

(hexamethylphosphoramide)

HMQC heteronuclear multiple quantum

correlation

HOMO highest occupied molecular orbital

HPLC high-performance liquid

chromatography; high-pressure

liquid chromatography

HPV human papilloma virus

HR heart rate

HRMS high-resolution mass spectrometry

HRT hormone replacement therapy

HSA human serum albumin

HSP heat shock protein

HSQC heteronuclear single quantum

correlation

22

HSV herpes simplex virus

HTS high throughput screening

Hz hertz

i-NOS inducible nitric oxide synthase

i-Pr isopropyl

IC50 half-maximum inhibitory

concentration

IBD inflammatory bowel disease

IBS irritable bowel syndrome

ICR ion cyclotron resonance

icv intracerebroventricular (dosing)

Ig immunoglobulin

iGluR ionotropic glutamate receptor

IHC immunohistochemistry

IM intramuscularly

INDO intermediate neglect of differential

overlap

ip intraperitoneally

IP ionization potential

IR infrared

it intrathecal

iv intravenous

IVUS intravascular ultrasound

J coupling constant (in NMR

spectrometry)

K kelvin(s) (absolute temperature)

k kilo

Ki inhibition constant

Km Michaelis constant

L liter(s)

LAH lithium aluminum hydride

LBD ligand binding domain

LC liquid chromatography

LC-MS liquid chromatography-mass

spectrometry

LCAO linear combination of atomic

orbitals

LD50 dose that is lethal in 50% of test

subjects

LDA lithium diisopropylamide; local

density approximation

LDL-C low-density lipoprotein cholesterol

LE ligand efficiency

LFER linear free energy relationship

LFT liver function test

LH luteinizing hormone

LHMDS lithium hexamethyldisilazane;

lithium bis(trimethylsilyl)amide

LHRH luteinizing hormone releasing

hormone

lit. literature value (abbreviation used

with period)

LogP logarithm of partition coefficient

LPS lipopolysaccharide

LTMP lithium 2,2,6,6-

tetramethylpiperidide

LTP long-term potentiation

LUMO lowest unoccupied molecular

orbital

M molar (moles per liter); mega

m multiplet (spectral); meter(s); milli;

isotopic mass; magnetic quantum

number (ESR and NMR

spectroscopy); meta; molal (mol

kg-1)

m-CPBA meta-chloroperoxybenzoic acid

m/z mass-to-charge ratio (not m/e)

M+ parent molecular ion

mAcChR muscarinic ACh receptor

MALDI matrix-assisted laser desorption

ionization

MAP mean arterial pressure

MAPK mitogen-activated protein kinase

max maximum

MCD magnetic circular dichroism

MCR multicomponent reaction

MCSCF multi-configuration self-consistent

field

MD molecular dynamics

MDR multidrug resistance

Me methyl

MED medium effective dose/minimum

efficacious dose

MEM (2-methoxyethoxy)methyl

Mes 2,4,6-trimethylphenyl (mesityl)

[not methylsulfonyl (mesyl)]

mGluR metabotropic glutamate receptor

MHC major histocompatibility complex

MHz megahertz

MIC minimal inhibitory concentration

min minute(s); minimum

mL milliliter

mM millimolar (millimoles per liter)

MMP matrix metalloproteinase

MO molecular orbital

MOA mechanism of action

mol mole(s); molecular (as in mol wt)

MOM methoxymethyl

mp melting point

MP Møller–Plesset perturbation theory

MRCI multi-reference configuration

interaction

MRSA methicillin-resistant

Staphylococcus aureus

MRI magnetic resonance imaging

mRNA messenger RNA

mRNA messenger ribonucleic acid

MRSA methicillin-resistant

Staphylococcus aureus

MS mass spectrometry

Ms methylsulfonyl (mesyl)

23

MTBE methyl tert-butyl ether

MTD maximum tolerated dose

MW, mol wt molecular weight

nAcChR nicotinic ACh receptor

NAD+ nicotinamide adenine dinucleotide

NADH reduced nicotinamide adenine

dinucleotide

NADP nicotinamide adenine dinucleotide

phosphate

NADPH reduced nicotinamide adenine

dinucleotide phosphate

NAM negative allosteric modulator

NBO natural bond orbital

NBS N-bromosuccinimide

NCE new chemical entity

NCI National Cancer Institute

NCS N-chlorosuccinimide

NDA new drug application

NE norepinephrine

NF-kB nuclear factor k B

NICS nucleus-independent chemical shift

NIH National Institutes of Health

nm nanometer(s)

NMDA N-methyl-D-aspartic acid

NME new molecular entity

NMO N-methylmorpholine-N-oxide

NMP N-methylpyrrolidone

NMR nuclear magnetic resonance

NNRTI non-nucleoside reverse

transcriptase inhibitor

NO nitric oxide

NOAEL no adverse effect level

NOE nuclear Overhauser effect

NOEL no-effect level

NOESY nuclear Overhauser effect

spectroscopy

NOS nitric oxide synthase

NPY neuropeptide Y

NRT natural resonance theory

NRTI nucleoside reverse transcriptase

inhibitor

NSAID non-steroidal anti-inflammatory

drug

NSCLC non-small cell lung cancer

Nu nucleophile

o ortho

obsd observed

OCT organic cation transporter

OD optical density

ORD optical rotary dispersion

p para

PAF platelet activating factor

PAGE polyacrylamide gel electrophoresis

PAM positive allosteric modulator

PAMPA parallel artificial membrane

permeability assay

PAS peripheral anionic site

PBO placebo

PBS phosphate buffered saline

PCA principle component analysis

PCC pyridinium chlorochromate

PCR polymerase chain reaction

PD pharmacodynamics; Parkinson's

disease

PDB Protein Data Bank

PDC pyridinium dichromate

PDE phosphodiesterase

PEG polyethylene glycol

PES photoelectron spectroscopy

PET positron emission tomography

P-gp P-glycoprotein

Ph phenyl

PI3K phosphoinositide 3-kinase

PIPES 1,4-piperazinediethanesulfonic

acid; piperazine-N,N’-bis(2-

ethanesulfonic acid)

PK pharmacokinetics

PKA protein kinase A

PKB protein kinase B

PKC protein kinase C

PLS partial least squares

pm picometer(s)

PM3 parametric method 3

PMB p-methoxybenzyl

PNS peripheral nervous system

po oral administration

PPA poly(phosphoric acid)

PPAR peroxisome proliferator-activated

receptor

PPB plasma protein binding

ppm part(s) per million

PPTS pyridinium para-toluenesulfonate

Pr propyl

PRH prolactin releasing hormone

PSA polar surface area

psi pounds per square inch

PT perturbation theory; prothrombin

time

PTT partial thromboplastin time

PTC phase-transfer catalysis

PTH parathyroid hormone

PXR pregnane X receptor

py pyridine

q quartet (spectral)

q.d. once daily ("quaque die")

q.i.d. four times a day (dosing) ("quater

in die")

QSAR quantitative structure–activity

relationship

QSPR quantitative structure-property

relationship

24

QW once a week (dosing)

RAS renin-angiotensin system

RBC red blood cell

RCM ring-closure metathesis

redox reduction–oxidation

Rf retention factor (in

chromatography)

RHF restricted Hartree–Fock

RIA radioimmunoassay

rmsd root mean square deviation

RNA ribonucleic acid

RO5 rule of five (Lipinski)

ROESY rotating frame Overhauser effect

spectroscopy

ROMP ring-opening metathesis

polymerization

ROS reactive oxygen species

rpm revolutions per minute

rRNA ribosomal ribonucleic acid

rt room temperature

s singlet (spectral); second(s)

s-Bu sec-butyl

SAHA suberoylanilide hydroxamic acid

SAR structure–activity relationship

SARM selective androgen receptor

modulator

SBDD structure-based drug discovery

SBP systolic blood pressure

sc subcutaneous

SCF self-consistent field

SDS sodium dodecyl sulfate

SEM scanning electron microscopy

SERM selective estrogen-receptor

modulator

SERT serotonin transporter

SET single electron transfer

SFC supercritical fluid chromatography

SIRT1 silent mating type information

regulation 2 homolog 1

SN' nucleophilic substitution with

allylic rearrangement

SN1 unimolecular nucleophilic

substitution

SN2 bimolecular nucleophilic

substitution

SNP single nucleotide polymorphism

SOMO single-occupied molecular orbital

SPECT single-photon emission computed

tomography

PR surface plasmon resonance;

stroboscopic pulse radiolysis

SSRI selective serotonin reuptake

inhibitor

T absolute temperature in units of

kelvins (K)

t time; temperature in units of

degrees Celsius (ºC)

t triplet (spectral)

t-Bu tert-butyl

t1/2 half-time

t.i.d. three times daily ("ter in die")

T2DM type 2 diabetes mellitus

TAE tris-acetate-EDTA

TB tuberculosis

TBAB tetrabutylammonium bromide

TBAC tetrabutylammonium chloride

TBAF tetrabutylammonium fluoride

TBHP tert-butyl hydroperoxide

TBS tert-butyldimethylsilyl

TCA trichloroacetic acid

TCA tricyclic antidepressant

TCNE tetracyanoethylene

TDDFT time-dependent density functional

theory

TEAB tetraethylammonium bromide

temp temperature

Tf trifluoromethanesulfonyl (triflyl)

TFA trifluoroacetic acid

TFAA trifluoroacetic anhydride

THF tetrahydrofuran

THP tetrahydropyran-2-yl

TIPS triisopropylsilyl

TK toxicokinetics

TLC thin-layer chromatography

TLR toll-like receptor

TMAI tetramethylammonium iodide

TMEDA N,N,N',N'-tetramethyl-1,2-

ethylenediamine

TMS trimethylsilyl; tetramethylsilane

TNF tumor necrosis factor

TNF-alpha tumor necrosis factor-alpha

TOF time of flight

TON turn over number (in catalysis) tR retention time (in chromatography)

Tr triphenylmethyl (trityl)

Tris tris(hydroxymethyl)aminomethane

tRNA transfer ribonucleic acid

Ts para-toluenesulfonyl (tosyl)

TS transition state

TSH thyroid stimulating hormone

TT thrombin time

UDP uridine 5'-diphosphate

UHF unrestricted Hartree–Fock

UHPLC ultra-high pressure liquid

chromatography

UV ultraviolet

v.i. see below (vide infra)

v.s. see above (vide supra)

v/v volume per unit volume (volume-

to-volume ratio)

VCD vibrational circular dichroism

25

VEGFR vascular endothelial growth factor

receptor

vis visible

viz. namely

VLDL very low density lipoprotein

vol volume

VRE vancomycin resistant enterococci

WBA whole body autoradiography

w/w weight per unit weight (weight-to-

weight ratio)

WT wild type

wt weight

XAFS X-ray absorption fine structure

spectroscopy

ZINDO Zerner parameterization of

intermediate neglect of

differential overlap

STANDARD AMINO ACID ABBREVIATIONS:

•The three-letter code or name may be used in the text.

•With a single amino acid, use the three-letter code (e.g., Met246).

•If more than one amino acid is specified, as in mutants or substitutions, use one-letter code

(S238H).

•When two or more amino acids are used in a string, use either the three-letter code or single

letter (e.g., His-Ile-Thr-Ser or HITS).

•For use of D amino acids, use the 3 letter abbreviation only (e.g., DAla)

alanine Ala A leucine Leu L

arginine Arg R lysine Lys K

asparagine Asn N methionine Met M

aspartic acid Asp D phenylalanine Phe F

cysteine Cys C proline Pro P

glutamic acid Glu E serine Ser S

glutamine Gln Q threonine Thr T

glycine Gly G tryptophan Trp W

histidine His H tyrosine Tyr Y

isoleucine Ile I valine Val V

Revised 12-15-11